{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T08:54:06Z","timestamp":1784883246544,"version":"3.55.0"},"reference-count":58,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft (DFG), Research Unit FOR-2558 \u201cTraceAge\u201d","award":["Scho 849\/6\u20131"],"award-info":[{"award-number":["Scho 849\/6\u20131"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG), Research Unit FOR-2558 \u201cTraceAge\u201d","award":["HA 4318\/4-2"],"award-info":[{"award-number":["HA 4318\/4-2"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG), Research Unit FOR-2558 \u201cTraceAge\u201d","award":["Scho 849\/7\u20131"],"award-info":[{"award-number":["Scho 849\/7\u20131"]}]},{"name":"SFB TR 296 \u201cLocoTact\u201d","award":["Scho 849\/6\u20131"],"award-info":[{"award-number":["Scho 849\/6\u20131"]}]},{"name":"SFB TR 296 \u201cLocoTact\u201d","award":["HA 4318\/4-2"],"award-info":[{"award-number":["HA 4318\/4-2"]}]},{"name":"SFB TR 296 \u201cLocoTact\u201d","award":["Scho 849\/7\u20131"],"award-info":[{"award-number":["Scho 849\/7\u20131"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Traumatic spinal cord injury (TSCI) profoundly impacts patients by precipitating a loss of motor and sensory capabilities, largely due to oxidative stress and inflammation during the secondary injury phase. Methods: This investigation explores the diagnostic potential of zinc (Zn) and free zinc (fZn) as biomarkers by analyzing their serum concentration dynamics in 48 TSCI individuals with TSCI, with the aim of correlating these levels with neurological impairment. Serum samples collected at admission, 4 h, 9 h, 12 h, 24 h, and 3 days post-injury were analyzed for total serum Zn and fZn concentrations. The patients were compared to a control group comprised of individuals with vertebral fractures but no neurological deficits. Results: The study revealed injury-specific fluctuations in Zn and fZn levels following TSCI, with significantly lower Zn levels observed post-TSCI compared to controls (p = 0.016). The American Spinal Injury Association (ASIA) Impairment scale (AIS) assessments at admission and three months post-injury showed Zn level differences are linked to neurological recovery (AIS+:1 &gt; AIS+:2, 0 h: p = 0.008; AIS+:0 &lt; AIS+:1, 4 h: p = 0.016), highlighting the critical role of Zn and trace elements in the early remission process after TSCI. Notably, significant differences in fZn levels were detected between the control and TSCI groups (TSCI &lt; Control; 12 h: p = 0.045; 24 h: p = 0.001; 3 d: p = 0.016), with the peak diagnostic performance of fZn at 24 h post-injury, as indicated by an Area Under the ROC Curve (AUC) of 83.84% (CI: 0.698\u20130.978). Conclusions: These findings underscore the potential of fZn as a biomarker to guide early diagnostic and therapeutic interventions aimed at mitigating secondary injury and enhancing recovery outcomes. This study contributes insights into the dynamics of serum Zn and its importance, holding specific diagnostic properties that could be critically relevant in the early phase of biomarker signature development for TSCI diagnostics and prognosis.<\/jats:p>","DOI":"10.3390\/nu17030496","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T11:10:39Z","timestamp":1738149039000},"page":"496","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Total and Free Zinc Dynamics as Biomarkers for Neurological Impairment in Traumatic Spinal Cord Injury"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8006-9742","authenticated-orcid":false,"given":"Raban Arved","family":"Heller","sequence":"first","affiliation":[{"name":"Institute for Experimental Endocrinology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie, Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, 13353 Berlin, Germany"},{"name":"Department of Food Chemistry and Toxicology, Technische Universit\u00e4t Berlin, Stra\u00dfe des 17. Juni 135, 10623 Berlin, Germany"},{"name":"Department of Traumatology and Orthopaedics, Septic and Reconstructive Surgery, Bundeswehr Hospital Berlin, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9140-2448","authenticated-orcid":false,"given":"Maria","family":"Maares","sequence":"additional","affiliation":[{"name":"Department of Food Chemistry and Toxicology, Technische Universit\u00e4t Berlin, Stra\u00dfe des 17. Juni 135, 10623 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7706-7906","authenticated-orcid":false,"given":"Thilo Samson","family":"Chillon","sequence":"additional","affiliation":[{"name":"Institute for Experimental Endocrinology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie, Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5767-7125","authenticated-orcid":false,"given":"Hanno","family":"Witte","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Bundeswehr Hospital Ulm, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Obada T.","family":"Al-Halabi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Medical Faculty, Heidelberg University, Grabengasse 1, 69117 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Heene","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Medical Faculty, Heidelberg University, Grabengasse 1, 69117 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8218-9243","authenticated-orcid":false,"given":"Alexander","family":"Younsi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Medical Faculty, Heidelberg University, Grabengasse 1, 69117 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Haubruck","sequence":"additional","affiliation":[{"name":"Raymond-Purves Bone and Joint Research Laboratories, Kolling Institute of Medical Research, Institute of Bone and Joint Research, University of Sydney, St Leonards, NSW 2065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9445-1555","authenticated-orcid":false,"given":"Lutz","family":"Schomburg","sequence":"additional","affiliation":[{"name":"Institute for Experimental Endocrinology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie, Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arash","family":"Moghaddam","sequence":"additional","affiliation":[{"name":"Orthopedic and Trauma Surgery, Frohsinnstra\u00dfe 12, 63739 Aschaffenburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahram","family":"Biglari","sequence":"additional","affiliation":[{"name":"Department of Paraplegiology, BG Trauma Centre Ludwigshafen, 67071 Ludwigshafen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1622-8718","authenticated-orcid":false,"given":"Hajo","family":"Haase","sequence":"additional","affiliation":[{"name":"Department of Food Chemistry and Toxicology, Technische Universit\u00e4t Berlin, Stra\u00dfe des 17. Juni 135, 10623 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1089\/neu.2004.21.1355","article-title":"A global perspective on spinal cord injury epidemiology","volume":"21","author":"Ackery","year":"2004","journal-title":"J. Neurotrauma"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Alizadeh, A., Dyck, S.M., and Karimi-Abdolrezaee, S. (2019). Traumatic Spinal Cord Injury: An Overview of Pathophysiology, Models and Acute Injury Mechanisms. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.00282"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1038\/s41393-020-0477-8","article-title":"\u201cTime is spine\u201d: The importance of early intervention for traumatic spinal cord injury","volume":"58","author":"Ahuja","year":"2020","journal-title":"Spinal Cord"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Gammoh, N.Z., and Rink, L. (2017). Zinc in Infection and Inflammation. Nutrients, 9.","DOI":"10.20944\/preprints201705.0176.v1"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.abb.2016.03.022","article-title":"Zinc and immunity: An essential interrelation","volume":"611","author":"Maares","year":"2016","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kijima, K., Ono, G., Kobayakawa, K., Saiwai, H., Hara, M., Yoshizaki, S., Yokota, K., Saito, T., Tamaru, T., and Iura, H. (2023). Zinc deficiency impairs axonal regeneration and functional recovery after spinal cord injury by modulating macrophage polarization via NF-kappaB pathway. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1290100"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1007\/s00775-011-0797-4","article-title":"Zinc homeostasis and signaling in health and diseases: Zinc signaling","volume":"16","author":"Fukada","year":"2011","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Maares, M., Hackler, J., Haupt, A., Heller, R.A., Bachmann, M., Diegmann, J., Moghaddam, A., Schomburg, L., and Haase, H. (2022). Free Zinc as a Predictive Marker for COVID-19 Mortality Risk. Nutrients, 14.","DOI":"10.3390\/nu14071407"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1007\/s10534-015-9858-4","article-title":"Alterations in zinc binding capacity, free zinc levels and total serum zinc in a porcine model of sepsis","volume":"28","author":"Hoeger","year":"2015","journal-title":"Biometals"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wessels, I., Maywald, M., and Rink, L. (2017). Zinc as a Gatekeeper of Immune Function. Nutrients, 9.","DOI":"10.3390\/nu9121286"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Heller, R.A., Sperl, A., Seelig, J., Haubruck, P., Bock, T., Werner, T., Besseling, A., Sun, Q., Schomburg, L., and Moghaddam, A. (2020). Zinc Concentration Dynamics Indicate Neurological Impairment Odds after Traumatic Spinal Cord Injury. Antioxidants, 9.","DOI":"10.2139\/ssrn.3572840"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1017\/S0029665100000781","article-title":"Zinc and the immune system","volume":"59","author":"Rink","year":"2000","journal-title":"Proc. Nutr. Soc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1136\/thoraxjnl-2019-213357","article-title":"Zinc supplementation ameliorates lung injury by reducing neutrophil recruitment and activity","volume":"75","author":"Wessels","year":"2020","journal-title":"Thorax"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6491","DOI":"10.4049\/jimmunol.181.9.6491","article-title":"Zinc signals are essential for lipopolysaccharide-induced signal transduction in monocytes","volume":"181","author":"Haase","year":"2008","journal-title":"J. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.ab.2006.02.009","article-title":"Flow cytometric measurement of labile zinc in peripheral blood mononuclear cells","volume":"352","author":"Haase","year":"2006","journal-title":"Anal. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4331625","DOI":"10.1155\/2021\/4331625","article-title":"Zinc Regulates Glucose Metabolism of the Spinal Cord and Neurons and Promotes Functional Recovery after Spinal Cord Injury through the AMPK Signaling Pathway","volume":"2021","author":"Hu","year":"2021","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9636897221109884","DOI":"10.1177\/09636897221109884","article-title":"Supplementation With Vitamin E, Zinc, Selenium, and Copper Re-Establishes T-Cell Function and Improves Motor Recovery in a Rat Model of Spinal Cord Injury","volume":"31","author":"Garcia","year":"2022","journal-title":"Cell Transpl."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.ebiom.2019.03.003","article-title":"The acute phase serum zinc concentration is a reliable biomarker for predicting the functional outcome after spinal cord injury","volume":"41","author":"Kijima","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"117351","DOI":"10.1016\/j.lfs.2020.117351","article-title":"Zinc promotes functional recovery after spinal cord injury by activating Nrf2\/HO-1 defense pathway and inhibiting inflammation of NLRP3 in nerve cells","volume":"245","author":"Li","year":"2020","journal-title":"Life Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1111\/cns.13460","article-title":"Zinc provides neuroprotection by regulating NLRP3 inflammasome through autophagy and ubiquitination in a spinal contusion injury model","volume":"27","author":"Lin","year":"2021","journal-title":"CNS Neurosci. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Haruta, Y., Kobayakawa, K., Saiwai, H., Hata, K., Tamaru, T., Iura, H., Ono, G., Kitade, K., Kijima, K., and Iida, K. (2022). Zinc chelator treatment in crush syndrome model mice attenuates ischemia-reperfusion-induced muscle injury due to suppressing of neutrophil infiltration. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-19903-0"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wu, D., Lewis, E.D., Pae, M., and Meydani, S.N. (2018). Nutritional Modulation of Immune Function: Analysis of Evidence, Mechanisms, and Clinical Relevance. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.03160"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s11064-022-03762-2","article-title":"Zinc Promotes Spinal Cord Injury Recovery by Blocking the Activation of NLRP3 Inflammasome Through SIRT3-Mediated Autophagy","volume":"48","author":"Xu","year":"2023","journal-title":"Neurochem. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1007\/s10571-022-01273-w","article-title":"Trehalose-Carnosine Prevents the Effects of Spinal Cord Injury Through Regulating Acute Inflammation and Zinc(II) Ion Homeostasis","volume":"43","author":"Paterniti","year":"2023","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.3945\/ajcn.110.008417","article-title":"A comparison of zinc metabolism, inflammation, and disease severity in critically ill infected and noninfected adults early after intensive care unit admission","volume":"93","author":"Besecker","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Maywald, M., Wang, F., and Rink, L. (2018). The Intracellular Free Zinc Level Is Vital for Treg Function and a Feasible Tool to Discriminate between Treg and Activated Th Cells. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113575"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Alker, W., Schwerdtle, T., Schomburg, L., and Haase, H. (2019). A Zinpyr-1-based Fluorimetric Microassay for Free Zinc in Human Serum. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20164006"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1039\/C9MT00177H","article-title":"A metalloproteomic analysis of interactions between plasma proteins and zinc: Elevated fatty acid levels affect zinc distribution","volume":"11","author":"Coverdale","year":"2019","journal-title":"Metallomics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.bbalip.2018.09.007","article-title":"Crosstalk between zinc and free fatty acids in plasma","volume":"1864","author":"Coverdale","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Doering, P., Stoltenberg, M., Penkowa, M., Rungby, J., Larsen, A., and Danscher, G. (2010). Chemical blocking of zinc ions in CNS increases neuronal damage following traumatic brain injury (TBI) in mice. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010131"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.burns.2019.08.012","article-title":"The impact of serum zinc normalization on clinical outcomes in severe burn patients","volume":"46","author":"Olson","year":"2020","journal-title":"Burns"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Han, M., Lin, W.H., Huang, S.H., Lin, Z.X., and Li, K.S. (2023). Association between plasma metal elements and platelet dysfunction in trauma-induced coagulopathy rat model. J. Trace Elem. Med. Biol., 79.","DOI":"10.1016\/j.jtemb.2023.127210"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1002\/jpen.2494","article-title":"Effect of zinc supplement on patients with trauma: A systematic review and meta-analysis","volume":"47","author":"Huang","year":"2023","journal-title":"J. Parenter. Enter. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"World Medical Association (2013). World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA, 310, 2191\u20132194.","DOI":"10.1001\/jama.2013.281053"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"g7594","DOI":"10.1136\/bmj.g7594","article-title":"Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): The TRIPOD statement","volume":"350","author":"Collins","year":"2015","journal-title":"BMJ"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Bock, T., Heller, R.A., Haubruck, P., Raven, T.F., Pilz, M., Moghaddam, A., and Biglari, B. (2021). Pursuing More Aggressive Timelines in the Surgical Treatment of Traumatic Spinal Cord Injury (TSCI): A Retrospective Cohort Study with Subgroup Analysis. J. Clin. Med., 10.","DOI":"10.3390\/jcm10245977"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3159","DOI":"10.1093\/brain\/awab203","article-title":"Predicting neurological recovery after traumatic spinal cord injury by time-resolved analysis of monocyte subsets","volume":"144","author":"Heller","year":"2021","journal-title":"Brain"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1007\/BF02221591","article-title":"A comprehensive classification of thoracic and lumbar injuries","volume":"3","author":"Magerl","year":"1994","journal-title":"Eur. Spine J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1467-9574.1970.tb00104.x","article-title":"Raised conditional level of significance for the 2 \u00d7 2-table when testing the equality of two probabilities","volume":"24","author":"Boschloo","year":"1970","journal-title":"Stat. Neerl."},{"key":"ref_40","unstructured":"R Core Team (2024). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_41","first-page":"1","article-title":"Package \u2018ggplot2\u2019","volume":"2","author":"Wickham","year":"2016","journal-title":"Creat. Elegant Data Vis. Using Gramm. Graphics. Version"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3023","DOI":"10.1080\/10408398.2020.1862048","article-title":"Zinc supplementation and immune factors in adults: A systematic review and meta-analysis of randomized clinical trials","volume":"62","author":"Jafari","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"155396","DOI":"10.1016\/j.cyto.2020.155396","article-title":"Zinc supplementation is associated with a reduction in serum markers of inflammation and oxidative stress in adults: A systematic review and meta-analysis of randomized controlled trials","volume":"138","author":"Hosseini","year":"2021","journal-title":"Cytokine"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ejphar.2018.07.019","article-title":"The effect of zinc supplementation on plasma C-reactive protein concentrations: A systematic review and meta-analysis of randomized controlled trials","volume":"834","author":"Mousavi","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1093\/neuros\/nyw080","article-title":"Traumatic Spinal Cord Injury-Repair and Regeneration","volume":"80","author":"Ahuja","year":"2017","journal-title":"Neurosurgery"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"491597","DOI":"10.4061\/2011\/491597","article-title":"Insight into Glutamate Excitotoxicity from Synaptic Zinc Homeostasis","volume":"2011","author":"Takeda","year":"2011","journal-title":"Int. J. Alzheimer\u2019s Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"9857201","DOI":"10.1155\/2016\/9857201","article-title":"Spinal Plasticity and Behavior: BDNF-Induced Neuromodulation in Uninjured and Injured Spinal Cord","volume":"2016","author":"Garraway","year":"2016","journal-title":"Neural Plast."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.3727\/096368915X686201","article-title":"The Role of Brain-Derived Neurotrophic Factor in Bone Marrow Stromal Cell-Mediated Spinal Cord Repair","volume":"24","author":"Ritfeld","year":"2015","journal-title":"Cell Transplant."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1007\/s10875-009-9298-4","article-title":"NK and NKT cells in aging and longevity: Role of zinc and metallothioneins","volume":"29","author":"Mocchegiani","year":"2009","journal-title":"J. Clin. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1399S","DOI":"10.1093\/jn\/130.5.1399S","article-title":"The dynamic link between the integrity of the immune system and zinc status","volume":"130","author":"Fraker","year":"2000","journal-title":"J. Nutr."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Maywald, M., Wessels, I., and Rink, L. (2017). Zinc Signals and Immunity. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18102222"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3458","DOI":"10.1016\/j.neuron.2022.10.020","article-title":"Microglia states and nomenclature: A field at its crossroads","volume":"110","author":"Paolicelli","year":"2022","journal-title":"Neuron"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.immuni.2013.02.012","article-title":"Recruitment of beneficial M2 macrophages to injured spinal cord is orchestrated by remote brain choroid plexus","volume":"38","author":"Shechter","year":"2013","journal-title":"Immunity"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Shechter, R., London, A., Varol, C., Raposo, C., Cusimano, M., Yovel, G., Rolls, A., Mack, M., Pluchino, S., and Martino, G. (2009). Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLoS Med, 6.","DOI":"10.1371\/journal.pmed.1000113"},{"key":"ref_55","first-page":"5388944","article-title":"Prophylactic Zinc Administration Combined with Swimming Exercise Prevents Cognitive-Emotional Disturbances and Tissue Injury following a Transient Hypoxic-Ischemic Insult in the Rat","volume":"2022","author":"Limon","year":"2022","journal-title":"Behav. Neurol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1080\/10790268.2022.2033578","article-title":"Systematic overviews of partnership principles and strategies identified from health research about spinal cord injury and related health conditions: A scoping review","volume":"46","author":"Hoekstra","year":"2023","journal-title":"J. Spinal Cord Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1089\/neu.2017.5036","article-title":"Facilitators and Barriers to International Collaboration in Spinal Cord Injury: Results from a Survey of Clinicians and Researchers","volume":"35","author":"Noonan","year":"2017","journal-title":"J. Neurotrauma"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1089\/neu.2020.7473","article-title":"Characterizing Natural Recovery after Traumatic Spinal Cord Injury","volume":"38","author":"Kirshblum","year":"2020","journal-title":"J. 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